Impact Factor 3.831

Frontiers journals are at the top of citation and impact metrics

Brief Research Report ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.01373

Downregulation of the Vitamin D Receptor Regulated Gene Set in the Hippocampus After MDMA Treatment

 Peter Petschner1*,  Noemi Balogh1, Csaba Adori1, Viola Tamasi2, Sahel Kumar1,  Gabriella Juhasz1, 3, 4 and  Gyorgy Bagdy1, 4
  • 1Faculty of Pharmacy, Department of Pharmacodynamics, Semmelweis University, Hungary
  • 2Department of Genetics, Cell and Immunobiology, Faculty of Medicine, Semmelweis University, Hungary
  • 3SE-NAP 2 Genetic Brain Imaging Migraine Research Group, Semmelweis University, Hungary
  • 4NAP-2-SE New Antidepressant Target Research Group, Semmelweis University, Hungary

The active ingredient of ecstasy, ±3,4-methylenedioximethamphetamine (MDMA), in addition to its initial reinforcing effects, induces selective and non-selective brain damage. Evidences suggest that the hippocampus (HC), a central region for cognition, may be especially vulnerable to impairments on the long-run, nevertheless, transcription factors that may precede and regulate such chronic changes remained uninvestigated in this region. In the current study, we used gene-set enrichment analysis to reveal possible transcription factor candidates responsible for enhanced vulnerability of HC after MDMA administration. Dark Agouti rats were intraperitoneally injected with saline or 15 mg/kg MDMA. Three weeks later HC gene expression was measured by Illumina whole-genome beadarrays and gene-set enrichment analysis was performed with MSigDB transcription factor sets. The number of significantly altered genes on the genome level (significance<0.001) in up/downregulated sets was also counted. MDMA upregulated one, and downregulated 13 gene sets in the HC of rats, compared to controls, including Pax4, Pitx2, FoxJ2, FoxO1, Oct1, Sp3, AP3, FoxO4 and vitamin D receptor (VDR)-regulated sets (q-value<0.05). VDR-regulated set contained the second highest number of significantly altered genes, including among others, Camk2n2, Gria3 and Grin2a. Most identified transcription factors are implicated in the response to ischemia confirming that serious hypoxia/ischemia occurs in the HC after MDMA administration, which may contribute to the selective vulnerability of this brain region. Moreover, our results also raise the possibility that vitamin D supplementation, in addition to the commonly used antioxidants, could be a potential alternative method to attenuate MDMA-induced chronic hippocampal impairments.

Keywords: Long-Term Potentiation, Hippocampus, Microarray, Gene Expression, ecstasy, Vitamin D

Received: 13 Sep 2018; Accepted: 08 Nov 2018.

Edited by:

Francisco Lopez-Munoz, Universidad Camilo José Cela, Spain

Reviewed by:

Renato Corradetti, Università degli Studi di Firenze, Italy
Luis A. Tellez, Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Mexico  

Copyright: © 2018 Petschner, Balogh, Adori, Tamasi, Kumar, Juhasz and Bagdy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Peter Petschner, Department of Pharmacodynamics, Semmelweis University, Faculty of Pharmacy, Budapest, 1089, Hungary, petschnerp@yahoo.com